Document Detail


Gene transfer to coronary artery bypass conduits.
MedLine Citation:
PMID:  12400762     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Gene therapy is a rational approach to prevention of stenosis in saphenous vein grafts used as conduits for coronary artery bypass grafting. To explore this possibility we developed methods for adenoviral-mediated gene transfer to canine saphenous veins. METHODS: During a single procedure, autogenous canine saphenous vein segments were transduced ex vivo and used as coronary artery bypass grafts. The proximal end of each vein was ligated, adenovirus containing the Escherichia coli beta-galactosidase gene (Ad.CMVLacZ) was delivered at titers of 2.5 x 10(9) or 5 x 10(9) plaque-forming units (pfu)/mL to the lumen through a distal heparin lock, and the segment was immersed in the viral solution for 1 hour at 37 degrees C. Control segments were exposed to diluent alone in an identical manner. Aortocoronary anastomoses were made using cardiopulmonary bypass. Transgene expression was assessed qualitatively and quantitatively after 3 days. RESULTS: Beta-galactosidase levels showed a dose-dependent increase: 0.00 +/- 0.00 ng/mg total protein for controls; 5.60 +/- 2.27 ng/mg total protein for a viral titer of 2.5 x 10(9) pfu/mL and 11.97 +/- 6.14 ng/mg for 5 x 10(9) pfu/mL. The two dosage groups differed significantly from each other (p = 0.035) and from controls (p = 0.003). X-gal staining demonstrated mostly endothelial and scattered adventitial transgene expression. CONCLUSIONS: Transgene expression after ex vivo gene transfer into saphenous vein grafts in a canine coronary artery bypass model indicates that this method may be useful for delivery of therapeutic genes to prevent or retard vein graft arteriosclerosis.
Authors:
Cynthia K Chiu-Pinheiro; Timothy O'Brien; Zvonimir S Katusic; Luis F Bonilla; Chad E Hamner; Hartzell V Schaff
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Annals of thoracic surgery     Volume:  74     ISSN:  0003-4975     ISO Abbreviation:  Ann. Thorac. Surg.     Publication Date:  2002 Oct 
Date Detail:
Created Date:  2002-10-28     Completed Date:  2002-11-26     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  15030100R     Medline TA:  Ann Thorac Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1161-6; discussion 1166     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / genetics
Animals
Coronary Artery Bypass*
Coronary Stenosis / prevention & control*
Dogs
Escherichia coli / genetics
Gene Transfer Techniques*
Male
Saphenous Vein*
Transgenes
beta-Galactosidase / genetics
Grant Support
ID/Acronym/Agency:
HL58080/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
EC 3.2.1.23/beta-Galactosidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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